scholarly journals Immunohistochemistry-Based Taxonomical Classification of Bladder Cancer Predicts Response to Neoadjuvant Chemotherapy

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1784 ◽  
Author(s):  
Albert Font ◽  
Montserrat Domènech ◽  
Raquel Benítez ◽  
Marta Rava ◽  
Miriam Marqués ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Complete Response ◽  
Tissue Microarrays ◽  
Tumor Subtypes ◽  
Significant Survival ◽  
Taxonomical Classification ◽  
Muscle Invasive

Background: Platinum-based neoadjuvant chemotherapy (NAC) increases the survival of patients with organ-confined urothelial bladder cancer (UBC). In retrospective studies, patients with basal/squamous (BASQ)-like tumors present with more advanced disease and have worse prognosis. Transcriptomics-defined tumor subtypes are associated with response to NAC. Aim: To investigate whether immunohistochemical (IHC) subtyping predicts NAC response. Methods: Patients with muscle-invasive UBC having received platinum-based NAC were identified. Tissue microarrays were used to type tumors for KRT5/6, KRT14, GATA3, and FOXA1. Outcomes: progression-free survival and disease-specific survival; univariable and multivariate Cox regression models were applied. Results: We found a very high concordance between mRNA and protein expression. Using IHC-based hierarchical clustering, we classified 126 tumors in three subgroups: BASQ-like (FOXA1/GATA3 low; KRT5/6/14 high), Luminal-like (FOXA1/GATA3 high; KRT5/6/14 low), and mixed-cluster (FOXA1/GATA3 high; KRT5/6 high; KRT14 low). Applying multivariable analyses, patients with BASQ-like tumors were more likely to achieve a pathological response to NAC (OR 3.96; p = 0.017). The clinical benefit appeared reflected in the lack of significant survival differences between patients with BASQ-like and luminal tumors. Conclusions: Patients with BASQ-like tumors—identified through simple and robust IHC—have a higher likelihood of undergoing a pathological complete response to NAC. Prospective validation is required.

scholarly journals Immunohistochemistry-based taxonomical classification of bladder cancer predicts response to neoadjuvant chemotherapy

2019 ◽  
Author(s):  
A. Font ◽  
M. Domènech ◽  
R. Benítez ◽  
M. Rava ◽  
M. Marqués ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cox Regression ◽  
Mutational Analysis ◽  
Pathological Complete Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Disease Specific Survival ◽  
Muscle Invasive ◽  
Disease Specific

ABSTRACTPlatinum-based neoadjuvant chemotherapy (NAC) increases the survival of patients with organ-confined urothelial bladder cancer (UBC). Because not all patients benefit from treatment, NAC has not been widely applied in the clinical setting. There is strong evidence, based on retrospective studies, that patients with Basal/Squamous (BASQ)-like tumours present with more advanced disease and have worse prognosis; global transcriptomics can identify tumour subtypes associated with response to NAC. We aimed to investigate whether tumour immunohistochemical (IHC) subtyping predicts NAC response. Patients with muscle-invasive UBC having received platinum-based NAC were identified in two hospitals in Spain. Tissue microarrays were constructed; RNA and DNA were extracted from full sections. Nanostring analysis and immunohistochemistry to identify BASQ-like tumours and mutational analysis of UBC oncogenes. We used hierarchical clustering to classify 126 tumours and adjusted logistic regression to assess association with treatment response. Outcomes were progression-free survival and disease-specific survival; univariable and multivariate Cox regression models were applied. We found very high concordance between mRNA and protein for the 4 markers analyzed. We identified three main subgroups: BASQ-like (FOXA1/GATA3 low; KRT5/6/14 high), Luminal-like (FOXA1/GATA3 high; KRT5/6/14 low), and mixed-cluster (FOXA1/GATA3 high; KRT5/6 high; KRT14 low). Patients with BASQ-like tumours were more likely to achieve a pathological response to NAC, displaying a disease-specific survival similar to that of the remaining patients. In conclusion, patients with BASQ-like tumours - identified through simple and robust immunohistochemistry - have a higher likelihood of undergoing a pathological complete response to NAC. Prospective validation in independent series is required.Novelty and impactNeoadjuvant chemotherapy is an important component of the management of patietns with muscle-invasive bladder cancer but improved stratification is necessary. This retrospective study shows that patients with BASQ-like tumors can be identified using immunohistochemistry on paraffin-embedded tissue and are 4-fold more likely to achieve a pathological complete response to platinum-based NAC. The disease-specific survival of patients with BASQ-like tumours treated with NAC was not different from that of other tumour subtypes.

scholarly journals Pathologic Response Rates of Gemcitabine/Cisplatin versus Methotrexate/Vinblastine/Adriamycin/Cisplatin Neoadjuvant Chemotherapy for Muscle Invasive Urothelial Bladder Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Franklin C. Lee ◽  
William Harris ◽  
Heather H. Cheng ◽  
Jaideep Shenoi ◽  
Song Zhao ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Urothelial Cancer ◽  
Response Rates ◽  
Complete Response ◽  
Pathologic Response ◽  
Urothelial Bladder Cancer ◽  
Urothelial Bladder ◽  
Muscle Invasive ◽  
Alternative Regimen

Objectives. To compare pathologic outcomes after treatment with gemcitabine and cisplatin (GC) versus methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) in the neoadjuvant setting.Methods. Data was retrospectively collected on 178 patients with T2-T4 bladder cancer who underwent radical cystectomy between 2003 and 2011. Outcomes of interest included those with complete response (pT0) and any response (≤pT1). Odds ratios were calculated using multivariate logistic regression.Results. Compared to those who did not receive neoadjuvant chemotherapy, there were more patients with complete response (28% versus 9%, OR 3.11 (95% CI: 1.45–6.64),P=0.03) and any response (52% versus 25%, OR 3.23 (95% CI: 1.21–8.64),P=0.01). Seventy-two patients received GC (n=41) or MVAC (n=31). CR was achieved in 29% and 22% of GC and MVAC patients, respectively (multivariate OR 0.39, 95% CI 0.10–1.58). Any response (≤pT1) was achieved in 56% of GC and 45% of MVAC patients (multivariate OR 0.45, 95% CI 0.12–1.71).Conclusions. We observed similar pathologic response rates for GC and MVAC neoadjuvant chemotherapy in this cohort of patients with muscle invasive urothelial cancer (MIBC). Our findings support the use of GC as an alternative regimen in the neoadjuvant setting.

Pathologic down-staging and complete pathologic response with gemcitabine and cisplatin neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma of the bladder.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 307-307
Author(s):  
Sarah P. Psutka ◽  
Aria F. Olumi ◽  
Adam S. Feldman ◽  
Philip James Saylor ◽  
Donald S. Kaufman ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Clinical Stage ◽  
Pathologic Complete Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Published Data ◽  
Free Survival ◽  
Carcinoma Of The Bladder ◽  
Muscle Invasive

307 Background: Neoadjuvant chemotherapy (NC) with MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) improves survival in muscle invasive urothelial cancer (MI−UC) with patients who achieve pathologic complete response (PCR) following radical cystectomy (RC). Gemcitabine/cisplatin (GC) NC is increasingly employed due to lower toxicity, however, its effectiveness as neoadjuvant therapy is controversial and multiple studies have reported poor utilization of this therapy, despite recent recommendations advocating for broader use. We describe pathologic and clinical outcomes following NC and RC. Methods: We retrospectively evaluated patients with MI−UC who received NC between 2003 and 2011 (n=38). Those who were treated with neoadjuvant radiation therapy (n= 15) were excluded. We compared initial clinical stage at surgery to final pathological stage and assessed overall−median progression free−survival. Mean follow−up was 25 months (SD 21.6, range 3 –76 months). Results: Twenty-three patients who received NC were included. Nineteen patients (82.6%) were treated with GC, 3 (13.0%) with MVAC, and 1 (4.3%) with gemcitabine/paclitaxel. The median time from start of NC to RC was 119 days (IQR 98.5−146). 10/19 (52.6%) patients treated with GC achieved PCR (pT0) from clinical stage T2 (n=5), cT3 (n=2) and cT4 (n=3), and 6 (31.2%) were downstaged to pT1 and pTIS from cT2. Two patients treated with MVAC were downstaged to pT1 and one achieved PCR. Median recurrence-free survival was 13 months (IQR 6−19 months) with 8 patients developing recurrent or metastatic UC following RC. At median follow-up of 19 months (IQR 8−31.2 months, Range 1−71 months), 15/23 (65.2%) patients were disease free, all of whom had received GC NC prior to cystectomy. Conclusions: Neoadjuvant GC for MI−UC was associated with a 52.6% PCR rate at RC and was well tolerated. These data compare favorably with published data on GC and MVAC as NC, and warrant further study.

Selective organ preservation with neoadjuvant chemotherapy in the treatment of muscle invasive transitional cell carcinoma (TCC) of the bladder.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 310-310
Author(s):  
Shaista Hafeez ◽  
Robert Anthony Huddart
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Partial Response ◽  
Poor Response ◽  
Complete Response ◽  
Radical Radiotherapy ◽  
Bladder Preservation ◽  
Platinum Based Chemotherapy ◽  
Muscle Invasive

310 Background: Radiotherapy has been previously associated with high treatment failure for those with muscle invasive bladder cancer. Evidence suggests modern organ sparing approaches may have favourable outcome in appropriately selected patients. We investigate whether response to neo-adjuvant chemotherapy can guide selection for bladder preservation and identify those patients likely to have greater success with radical radiotherapy treatment. Methods: Retrospective analysis of 94 patients with T2-T4aN0M0 bladder TCC treated between January 2000 and June 2011. Patients received platinum based chemotherapy following transuretheral resection of bladder tumour, with repeat cystoscopy (+biopsy) performed to guide subsequent management. Poor responders were advised to proceed with surgery. We report on the outcome of 79 individuals who received radiotherapy. Results: 56 (60%) patients achieved complete response following chemotherapy (72% with stage T2). 15 (16%) patients achieved partial pathological response. 12 patients had radiological assessment of partial response made. 11 patients had poor response. All patients achieving complete response, 22 with partial response and 1 with poor response proceeded to radical radiotherapy. Median time to disease progression following radiotherapy was 17months (range 8-91). 5 patients developed invasive recurrence, 17 developed superficial recurrence, 4 developed local nodal disease and 7 developed metastasises. After median follow-up of 36 months (range 6-114), 50 patients were alive with no disease, 24 had died (14 from metastatic bladder cancer and 10 from other causes). 5 patients were alive with active disease (4 with localized and 1 with metastatic disease). 13 required cystectomy (9 for superficial disease, 3 for invasive recurrence, and 1 for treatment related toxicity). Of those alive and disease free 84% had an intact bladder. 82% had an intact bladder at last follow-up or death. Conclusions: Neoadjuvant chemotherapy followed by radical radiotherapy allows bladder preservation in over 80% of selected patients with survival rates comparable to contemporary surgical series.

Using radiologic response to predict prognosis in patients with muscle-invasive bladder cancer undergoing carboplatin-based neoadjuvant chemotherapy.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 361-361
Author(s):  
Shingo Hatakeyama ◽  
Hayato Yamamoto ◽  
Akiko Okamoto ◽  
Atsushi Imai ◽  
Takahiro Yoneyama ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Multivariate Analysis ◽  
Neoadjuvant Chemotherapy ◽  
Radical Cystectomy ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Contrast Enhanced Ct ◽  
Muscle Invasive

361 Background: Prognosis and tumor responses of carboplatin-based neoadjuvant chemotherapy for muscle invasive bladder cancer (MIBC) are not well documented. To assess the usefulness of carboplatin-based neoadjuvant chemotherapy, we examined the correlation between radiological responses and pathologic down staging on radical cystectomy (RCx) specimens, disease free survival (DFS), and overall survival (OS). Methods: Between March 2005 and June 2013, we performed carboplatin-based neoadjuvant chemotherapy followed by radical cystectomy in 115 patients with T2-4NxM0 MIBC. After diagnostic TUR biopsy, all participants received two courses of Gemcitabine plus Carboplatin therapy. Baseline and post chemotherapy tumor size from contrast enhanced CT were reviewed. The patients were divided in two groups between responders (CR+PR), and non-responders (SD+PD). RCx and bilateral pelvic lymphadenectomy were performed approximately within a month after cessation of chemotherapy. DFS and OS distributions within radiologic response subgroups were estimated with the Kaplan-Meier method and compared using the log-rank test. To evaluate independent predictor for DFS and OS, age, gender, performance status, pathological T and N stage, down-staging, tumor grade, renal function, and radiological responses were applied by Cox-regression multivariate analysis. Results: No significant differences were observed in patient backgrounds between the groups. Radiologic responses were observed in 75 (65%) patients with 69±24% decrease in responder group, whereas tumor response was 2.8±14% in non-responders. The rate of pathological down staging to <pT2 was 37 (49%) in responders, 5 (13%) in non-responders group. Radiologic response was a strong predictor of DFS and OS. A 5-year advantages of DFS and OS in responders vs. non-responders were 88% and 86% vs. 64% and 69%, respectively (P=0.021 and P=0.013). Multivariate analysis showed radiologic response was the independent factor for DFS and OS. Conclusions: Radiological response post carboplatin-based neoadjuvant chemotherapy is associated with OS in patients with MIBC.

Identifying predictors of pathologic complete response to neoadjuvant chemotherapy for muscle invasive bladder cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16015-e16015
Author(s):  
Andrea Harzstark ◽  
Maqdooda Merchant
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Radical Cystectomy ◽  
Clinical Stage ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Bivariate Analysis ◽  
Limited Information ◽  
Split Dose ◽  
Muscle Invasive

e16015 Background: Pathologic complete response (pCR) to neoadjuvant chemotherapy is associated with improved outcome in patients (pts) with muscle invasive and/or lymph node positive (LN+) bladder cancer. Although molecular predictors are currently being evaluated, limited information is available regarding purely clinical parameters offering predictive information regarding pCR to neoadjuvant chemotherapy. Methods: We identified 189 unique pts within Kaiser Permanente Northern California diagnosed with bladder cancer during 1/1/10 through 12/31/17 who underwent chemotherapy with neoadjuvant intent with a plan for subsequent radical cystectomy. All pts had disease that was ≥cT2 and/or ≥cN1 and M0. Fourteen variables were examined for their association with pCR at radical cystectomy, using bivariate analysis and multivariate models. Results: Of the 189 pts in our cohort, 141 (74.6%) were male, 162 (85.7%) were white and the mean age was 66.4 years. 76 (40.2%) pts achieved pCR; of these, 59 (77.6%) had pre-treatment hemoglobin (hg) ≥ 13 g/dL (p = 0.0087), 69 (90.8%) did not have hydronephrosis (p < 0.0001), 66 (86.8%) had no lymphovascular invasion (LVI) on transurethral resection of bladder tumor (TURBT) (p = 0.0506) and 69 (90.8%) had cT2 disease at time of diagnosis (p < 0.0001). Logistic regression analysis showed that pCR was associated with hg ≥ 13 (OR 2.736, 95% CI 1.188-6.657), absence of hydronephrosis (OR 4.672, 95% CI 1.820-13.554), age ≤ 75 years (OR 3.410, 95% CI 1.263-10.057), absence of LVI on TURBT (OR 2.592, 95% CI 1.055-6.829), and clinical stage T2 vs. ≥T3 and/or N+ (OR 6.480, 95% CI 2.645-17.858). There was no statistically significant relationship between pCR and the following variables: cumulative cisplatin dose, split dose chemotherapy, chemotherapy regimen, history of tobacco use, race, gender, Charlson comorbidity score, baseline alkaline phosphatase, and percentage body weight loss during therapy. Conclusions: Pathologic CR was predicted by Hg < 13 g/dL, absence of hydronephrosis, age ≤ 75 yrs, absence of LVI on TURBT specimen, and stage at diagnosis. These factors may influence selection of pts with muscle invasive and/or LN+ bladder cancer for neoadjuvant chemotherapy.

Sign in / Sign up

Export Citation Format

Share Document